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Hypertonic saline-dextran suppresses burn-related cytokine secretion by cardiomyocytes
J W Horton1, D L Maass, J White
1Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9160, USA. JURETA.HORTON@utsouthwestern.edu
Insights
Hypertonic saline-dextran (HSD) improves heart function after burn trauma by reducing inflammatory cytokine release from cardiomyocytes. This treatment mitigates burn-induced cardiac dysfunction and inflammation.
Area of Science:
- Cardiology
- Trauma Research
- Molecular Biology
Background:
- Burn trauma impairs cardiac function.
- Hypertonic saline-dextran (HSD) improves cardiac function post-burn.
- The cardioprotective mechanisms of HSD are not fully understood.
Purpose of the Study:
- To investigate if HSD alters cardiomyocyte tumor necrosis factor-alpha (TNF-alpha) secretion.
- To determine the effect of HSD on cardiac contraction and relaxation after burn injury.
- To elucidate the role of inflammatory cytokines in HSD-mediated cardioprotection.
Main Methods:
- Wistar-Furth rats underwent burn injury and received either saline or HSD.
- Hearts were isolated 24 hours post-burn for Langendorff perfusion or cardiomyocyte preparation.
- Cardiomyocytes were stimulated with lipopolysaccharide (LPS) to measure cytokine secretion.
Main Results:
- Burn trauma increased cardiomyocyte secretion of TNF-alpha, IL-1 beta, and IL-6, and worsened cardiac contraction.
- HSD treatment in burn-injured rats reduced cardiomyocyte cytokine secretion and LPS-induced inflammatory response.
- HSD treatment improved ventricular function in burn-injured rats.
Conclusions:
- HSD downregulates cardiomyocyte inflammatory cytokine secretion after burn trauma.
- Reduced cytokine secretion contributes to HSD-mediated cardioprotection.
- HSD offers a potential therapeutic strategy for burn-induced cardiac dysfunction.
Abstract:
Whereas hypertonic saline-dextran (HSD, 7.5% NaCl in 6% D70) improves cardiac contractile function after burn trauma, the mechanisms of HSD-related cardioprotection remain unclear. We recently showed that cardiomyocytes secrete tumor necrosis factor-alpha (TNF-alpha), a response that was enhanced by burn trauma. This study addressed the question: does HSD modulate cardiac contraction/relaxation by altering cardiomyocyte TNF-alpha secretion? Wistar-Furth rats (325 g) were given a burn injury over 40% of the total body surface area and were then randomized to receive a bolus of either isotonic saline or HSD (4 ml/kg, n = 14 rats/group). Sham burn rats were given either isotonic saline or HSD (n = 14 rats/group) to provide appropriate controls for the two burn groups. Hearts were isolated 24 h postburn for either Langendorff perfusion (n = 8 hearts/group) or to prepare cardiomyocytes (n = 6 hearts/group). Myocytes were stimulated with lipopolysaccharide (LPS) (0, 10, 25, or 50 microg for 18 h) to measure cytokine secretion. Burn trauma increased myocyte TNF-alpha and interleukin-1 beta and -6 secretion, exacerbated cytokine response to LPS stimulus, and impaired cardiac contraction. HSD treatment of burns decreased cardiomyocyte cytokine secretion, decreased responsiveness to LPS challenge with regard to cytokine secretion, and improved ventricular function. These data suggest that HSD mediates cardioprotection after burn trauma, in part, by downregulating cardiomyocyte secretion of inflammatory cytokines.